PLEKHG6
protein-codingpleckstrin homology and RhoGEF domain containing G6, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing
Gene summary
Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction. Implicated in cystic fibrosis. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLEKHG6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001384598.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 3 | 4 | |||
| missense | 169 | 12 | 181 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 171 | 15 | 0 | 186 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001371527.1 | 15 | MANE Select | |
| Ensembl | ENSP00000506982.1 | 15 | MANE Select | |
| RefSeq | NP_001138328.1 | 15 | Standard | |
| RefSeq | NP_001138329.2 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of RhoA activity
Biological Process
- regulation of Rho protein signal transduction
- positive regulation of GTPase activity
Molecular Function
- Rho guanyl-nucleotide exchange factor activity
- GTPase activator activity
- protein binding
Cellular Component
- spindle pole
- cytoplasm
- centrosome
- microvillus
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396988
- Coding exons
- 15
- Length
- 18071
- Individuals with no LoFs
- 125656
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 91
- Defined
- 125748
- p
- 0.000366
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.000607 | 462 | 462 | 1.00 | 0.0000291 | 4975 |
| Missense (PolyPhen) | 71 | 94.277 | 0.7531 | 1053 | ||
| Synonymous | -0.680 | 200 | 188 | 1.06 | 0.0000109 | 1691 |
| Loss of Function | 1.55 | 35 | 46.4 | 0.755 | 0.00000330 | 410 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0.00027 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00039 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00032 | 0.00031 | rare |
| South Asian | 0.0014 | 0.0013 | notable |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor activating the small GTPase RHOA, which, in turn, induces myosin filament formation. Also activates RHOG. Does not activate RAC1, or to a much lower extent than RHOA and RHOG. Part of a functional unit, involving PLEKHG6, MYH10 and RHOA, at the cleavage furrow to advance furrow ingression during cytokinesis. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with EZR, required for normal macropinocytosis. {ECO:0000269|PubMed:16721066, ECO:0000269|PubMed:17881735}.;
Recessive Scores
- pRec
- 0.0857
Intolerance Scores
- LoFtool
- 0.984
- RVIS EVS
- -0.79
- RVIS percentile EVS
- 12.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.296
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |